This invention relates to a mass spectrometer, and more particularly to a liquid chromatograph-coupled mass spectrometer, that is, liquid chromatograph/mass spectrometer, suitable for separating and analyzing a broad range of important non-volatile compounds in a living body, such as amines, amino acids, steroids, antibiotics, sugars, peptides, vitamins, etc.
Now, development of separation and analyzing techniques for the compounds relating to the living body is one of the important tasks in the analytical field. To this end, a liquid chromatograph having a distinguished separation ability coupled with a mass spectrometer having a distinguished identification ability has been under extensive development.
In FIG. 11, an entire structure of liquid chromatograph/mass spectrometer, where a double focusing mass spectrometer containing an electric field analyzing section 4 and a magnetic field analyzing section 5 is used in the mass analyzing region is shown to help understand the working principle of the liquid chromatograph/mass spectrometer.
A sample in the solution, separated by and eluted from a liquid chromatograph 1 is introduced into an ion source 3 through a line 2. Ions of sample molecules formed in the ion source 3 are introduced into a vacuum through an aperture and further into a mass analyzing region comprising an electric field analyzing section 4 and a magnetic field analyzing section 5 and mass analyzed. The mass analyzed ions are detected by an ion detector 6 and the detected information is led to a data processing section 7. The mass analyzing region comprising the electric field analyzing section 4 and the magnetic field analyzing section 5 is evacuated by an appropriate pumping system 9. Numeral 8 is a power source for the ion source 3, and numeral 10 is a signal transmission line. The working principle itself of a liquid chromatograph/mass spectrometer is simple, as described above, but the liquid chromatograph handles a sample in a liquid solution state, whereas the mass spectrometer handles a sample in a gaseous state. That is, there is an incompatibility therebetween, and thus the development of liquid chromatograph/mass spectrometer is a very difficult problem.
In order to solve the difficult problem, several methods have been proposed, typical of which are an atmospheric pressure ionization method disclosed in Japanese Patent Application Kokai (Laid-open) No. 60-127453 and a thermospray method disclosed in Analytical Chemistry, Vol. 55, No. 4, April, 1983, pp. 750-754.
As shown in FIG. 12, the atmospheric pressure ionization method comprises nebulizing solutions eluted from a liquid chromatograph by nebulization by means of a heated capillary 11 or by ultrasonic nebulization, further heating the nebulized solutions by a heated block 12, thereby vaporizing the nebulized solutions, ionizing the vaporized sample molecules by corona discharge by means of a needle electrode 13 and by a series of successive ion-molecule reactions, introducing the thus formed ions into a vacuum through a first aperture 14 and a second aperture 15 and mass analyzing the ions. The atmospheric pressure ionization method is characteristic of a high sensitivity and easy coupling with a liquid chromatograph because the ion source works under the atmospheric pressure. Intense molecular ions can be obtained from low-polar amines, steroids, antibiotics, etc. among the important, non-volatile compounds in the living body and can be mass analyzed, but molecular ions are less obtainable from high-polar sugars and peptides and are hard to mass analyze.
On the other hand, as shown in FIG. 13, the thermospray method comprises spraying solutions containing both samples and buffers like ammonium acetate from a heated capillary 11' into a vacuum of a few Torr or less, introducing ions formed by vaporization of the thus formed droplets into a mass analyzing region through a second aperture 15 and mass analyzing the ions in the mass analyzing region. In contrast to the atmospheric pressure ionization method, the thermospray method can analyze high-polar compounds such as sugars and peptides, but low-polar compounds such as amines, steroids, antibiotics, etc. are hard to analyze.
Thus, it seems that a broad range of important compounds relating to the living body can be analyzed by developing a liquid chromatograph/mass spectrometer provided with such two ion sources. A combined ion source having an ionization function based on such two ion sources seems to have such a structure, for example, as shown in FIG. 14. However, the following new problems are brought about by the essential difference between the atmospheric pressure ionization method working under the atmospheric pressure and the thermospray method working under a pressure as low as a few Torr.
1) The structure of combined ion source is complicated, because when the atmospheric pressure ionization method is used, a valve (not shown in the drawing) must be provided so that no liquid may leak out of a capillary 11' used in the thermospray method, whereas when the thermospray method is used, a valve (not shown in the drawing) must be provided so that no gas may leak out of an aperture for introducing the ions formed by the atmospheric pressure ionization method.
2) The atmospheric pressure ionization method requires no liquid nitrogen trap, etc. to prevent the pumping system from contaminations due to the eluate from the liquid chromatograph, whereas the thermospray method requires the trap (not shown in the drawing) and continuous analyzing operation must be discontinued to wash the trap at intervals of a few hours.
3) In case of the thermospray method, the inside of the ion source is always exposed to a large volume of gas and thus has a high chance for the contamination.